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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Formulation of Extended-Release Beads of Lamotrigine Based on Alginate and Cassia fistula Seed Gum by QbD Approach

Author(s): Dixita Jain, Akshay Sodani, Swapnanil Ray, Pranab Ghosh and Gouranga Nandi*

Volume 17, Issue 5, 2020

Page: [422 - 437] Pages: 16

DOI: 10.2174/1567201817666200317124022

Price: $65

Abstract

Aim: This study was focused on the formulation of the multi-unit extended-release peroral delivery device of lamotrigine for better management of epilepsy.

Background: The single-unit extended-release peroral preparations often suffer from all-or-none effect. A significant number of multi-unit delivery systems have been reported as a solution to this problem. But most of them are found to be composed of synthetic, semi-synthetic or their combination having physiological toxicity as well as negative environmental impact. Therefore, fabrication and formulation of multi-unit extended-release peroral preparations with natural, non-toxic, biodegradable polymers employing green manufacturing processes are being appreciated worldwide.

Objective: Lamotrigine-loaded extended-release multi-unit beads have been fabricated with the incorporation of a natural polysaccharide Cassia fistula seed gum in calcium-cross-linked alginate matrix employing a simple green process and 23 full factorial design.

Methods: The total polymer concentration, polymer ratio and [CaCl2] were considered as independent formulation variables with two different levels of each for the experiment-design. The extended-release beads were then prepared by the ionotropic gelation method using calcium chloride as the crosslinkerions provider. The beads were then evaluated for drug encapsulation efficiency and drug release. ANOVA of all the dependent variables such as DEE, cumulative % drug release at 2h, 5h, 12h, rate constant and dissolution similarity factor (f2) was done by 23 full factorial design using Design-Expert software along with numerical optimization of the independent variables in order to meet USP-reference release profile.

Results: The optimized batch showed excellent outcomes with DEE of 84.7 ± 2.7 (%), CPR2h of 8.41± 2.96 (%), CPR5h of 36.8± 4.7 (%), CPR12h of 87.3 ± 3.64 (%) and f2 of 65.9.

Conclusion: This approach of the development of multi-unit oral devices utilizing natural polysaccharides might be inspiring towards the world-wide effort for green manufacturing of sustained-release drug products by the QbD route.

Keywords: Lamotrigine, extended-release, multi-unit, beads, Cassia fistula seed gum, epilepsy.

Graphical Abstract
[1]
Tompson, D.J.; Ali, I.; Oliver-Willwong, R.; Job, S.; Zhu, L.; Lemme, F.; Hammer, A.E.; Vuong, A.; Messenheimer, J.A. Steady-state pharmacokinetics of lamotrigine when converting from a twice-daily immediate-release to a once-daily extended-release formulation in subjects with epilepsy (The COMPASS Study). Epilepsia, 2008, 49(3), 410-417.
[http://dx.doi.org/10.1111/j.1528-1167.2007.01274.x] [PMID: 17825077]
[2]
Yuen, A.W. Lamotrigine: a review of antiepileptic efficacy. Epilepsy, 1994, 35(5), 33-36.
[3]
Gunda, R.K.; Kumar, J.N.S.; Babu, C.A.; Anjaneyulu, M.V. Formulation development and evaluation of lamotrigine sustained release tablets using 32 facorial design. Int. J. Pharm. Sci. Res., 2015, 6(4), 1746-1752.
[4]
Błaszczyk, B.; Czuczwar, S.J. Efficacy, safety, and potential of extended-release lamotrigine in the treatment of epileptic patients. Neuropsychiatr. Dis. Treat., 2010, 6, 145-150.
[PMID: 20505846]
[5]
Werz, M.A. Pharmacotherapeutics of epilepsy: use of lamotrigine and expectations for lamotrigine extended release. Ther. Clin. Risk Manag., 2008, 4(5), 1035-1046.
[http://dx.doi.org/10.2147/TCRM.S3343] [PMID: 19209284]
[6]
Ramey, P.; Osborn, M.; Abou-Khalil, B. Conversion from immediate release to extended-release lamotrigine improves seizure control. Epilepsy Res., 2014, 108(9), 1637-1641.
[http://dx.doi.org/10.1016/j.eplepsyres.2014.08.004] [PMID: 25205163]
[7]
Bialer, M. Extended-release formulations for the treatment of epilepsy. CNS Drugs, 2007, 21(9), 765-774.
[http://dx.doi.org/10.2165/00023210-200721090-00005] [PMID: 17696575]
[8]
Rheims, S.; Ryvlin, P. Once-daily lamotrigine extended release for epilepsy management. Expert Rev. Neurother., 2009, 9(2), 167-173.
[http://dx.doi.org/10.1586/14737175.9.2.167] [PMID: 19210192]
[9]
Poonuru, R.R.; Gonugunta, C.S.R. Bimodal gastroretentive drug delivery systems of lamotrigine: formulation and evaluation. Indian J. Pharm. Sci., 2014, 76(6), 476-482.
[PMID: 25593380]
[10]
Mohammadi-Samani, S.; Jalali, F.; Tavakoli, S.; Ahmadi, F. Solid lipid microparticles of lamotrigine: an injectible controlled release system for local delivery in nerve injuries. J. Dr. Del. Sci. Technol., 2014, 24(4), 367-372.
[11]
Taksande, J.B.; Wadher, K.J.; Trivedi, R.V.; Umekar, M.J. Development and evaluation of lamotrigine loaded N-trimethyl chitosan microspheres for intranasal administration. Int. J. Chemtech Res., 2017, 10(2), 1-13.
[12]
Saini, T.R.; Drabu, S.; Ahmad, F.J.; Khatri, S. Preparation and in vitro evaluation of polylactic acid microspheres containing lamotrigine. Asian J. Chem., 2009, 21(6), 4413-4418.
[13]
Allen, L.V. Lamotrigine 1mg/ml oral suspension. US Pharm., 2015, 40(5), 64-65.
[14]
Mishra, B.; Sahoo, B.L.; Mishra, M.; Shukla, D.; Kumar, V. Design of a controlled release liquid formulation of lamotrigine. Daru, 2011, 19(2), 126-137.
[PMID: 22615649]
[15]
Siepmann, J.; Siepmann, F. Microparticles used as drug delivery systems. Prog. Colloid Polym. Sci., 2006, 133, 15-21.
[16]
Nidhi, ; Rashid, M.; Kaur, V.; Hallan, S.S.; Sharma, S.; Mishra, N. Microparticles as controlled drug delivery carrier for the treatment of ulcerative colitis: A brief review. Saudi Pharm. J., 2016, 24(4), 458-472.
[http://dx.doi.org/10.1016/j.jsps.2014.10.001] [PMID: 27330377]
[17]
Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G. Microencapsulation: A promising technique for controlled drug delivery. Res. Pharm. Sci., 2010, 5(2), 65-77.
[PMID: 21589795]
[18]
Soni, S.R.; Ghosh, A. Exploring pullulan-poly(vinyl alcohol) interpenetrating network microspheres as controlled release drug delivery device. Carbohydr. Polym., 2017, 174, 812-822.
[http://dx.doi.org/10.1016/j.carbpol.2017.07.016] [PMID: 28821135]
[19]
Ravella, V.N.; Nadendla, R.R.; Kesari, N.C. Design and evaluation of sustained release pellets of aceclofenac. J. Pharm. Res., 2013, 6, 525-531.
[http://dx.doi.org/10.1016/j.jopr.2013.04.040]
[20]
Sanchez-Ballester, N.M.; Soulairol, I.; Bataille, B.; Sharkawi, T. Flexible heteroionic calcium-magnesium alginate beads for controlled drug release. Carbohydr. Polym., 2019, 207, 224-229.
[http://dx.doi.org/10.1016/j.carbpol.2018.11.096] [PMID: 30600003]
[21]
Nayak, A.K.; Das, B.; Maji, R. Calcium alginate/gum Arabic beads containing glibenclamide: development and in vitro characterization. Int. J. Biol. Macromol., 2012, 51(5), 1070-1078.
[http://dx.doi.org/10.1016/j.ijbiomac.2012.08.021] [PMID: 22947454]
[22]
Sinha, P.; Ubaidulla, U.; Hasnain, M.S.; Nayak, A.K.; Rama, B. Alginate-okra gum blend beads of diclofenac sodium from aqueous template using ZnSO4 as a cross-linker. Int. J. Biol. Macromol., 2015, 79, 555-563.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.04.067] [PMID: 25987461]
[23]
Mandal, S.; Basu, S.K.; Sa, B. Ca2+ ion cross-linked interpenetrating network matrix tablets of polyacrylamide-grafted-sodium alginate and sodium alginate for sustained release of diltiazem hydrochloride. Carbohydr. Polym., 2010, 82, 867-873.
[http://dx.doi.org/10.1016/j.carbpol.2010.06.009]
[24]
Nayak, A.K.; Pal, D.; Pradhan, J.; Hasnain, M.S. Fenugreek seed mucilage-alginate mucoadhesive beads of metformin HCl: Design, optimization and evaluation. Int. J. Biol. Macromol., 2013, 54, 144-154.
[http://dx.doi.org/10.1016/j.ijbiomac.2012.12.008] [PMID: 23246901]
[25]
Nayak, A.K.; Pal, D.; Santra, K. Swelling and drug release behavior of metformin HCl-loaded tamarind seed polysaccharide-alginate beads. Int. J. Biol. Macromol., 2016, 82, 1023-1027.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.10.027] [PMID: 26472516]
[26]
Nandi, G.; Nandi, A.K.; Khan, N.S.; Pal, S.; Dey, S. Tamarind seed gum-hydrolyzed polymethacrylamide-g-gellan beads for extended release of diclofenac sodium using 32 full factorial design. Int. J. Biol. Macromol., 2018, 114, 214-225.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.03.064] [PMID: 29567498]
[27]
Rai, P.R.; Tiwary, A.K.; Rana, V. Superior disintegrating properties of calcium cross-linked Cassia fistula gum derivatives for fast dissolving tablets. Carbohydr. Polym., 2012, 87, 1098-1104.
[http://dx.doi.org/10.1016/j.carbpol.2011.08.050]
[28]
Huanbutta, K.; Sittikijyothin, W. Development and characterization of seed gums from Tamarindus indica and Cassia fistula as disintegrating agent for fast disintegrating Thai cordial tablet. Asian J. Pharm. Sci., 2017, 12(4), 370-377.
[http://dx.doi.org/10.1016/j.ajps.2017.02.004] [PMID: 32104348]
[29]
Huanbutta, K.; Sittikijyothin, W. Use of seed gums from Tamarindus indica and Cassia fistula as controlled-release agents. Asian J. Pharm. Sci., 2018, 13(5), 398-408.
[http://dx.doi.org/10.1016/j.ajps.2018.02.006] [PMID: 32104414]
[30]
Rai, P.R.; Tiwary, A.K.; Rana, V. Optimization of an aqueous tablet-coating process containing carboxymethylated Cassia fistula gum. AAPS PharmSciTech, 2012, 13(2), 431-440.
[http://dx.doi.org/10.1208/s12249-012-9763-x]
[31]
Nandi, G.; Changder, A.; Ghosh, L.K. Graft-copolymer of polyacrylamide-tamarind seed gum: Synthesis, characterization and evaluation of flocculating potential in peroral paracetamol suspension. Carbohydr. Polym., 2019, 215, 213-225.
[http://dx.doi.org/10.1016/j.carbpol.2019.03.088] [PMID: 30981348]
[32]
Varelas, C.G.; Dixon, D.G.; Steiner, C. Zero order release from biphasic polymer hydrogels. J. of Contr. Rel., 1995, 34, 185-192.
[http://dx.doi.org/10.1016/0168-3659(94)00085-9]
[33]
Gibaldi, M.; Feldman, S. Establishment of sink conditions in dissolution rate determinations. Theoretical considerations and application to nondisintegrating dosage forms. J. Pharm. Sci., 1967, 56(10), 1238-1242.
[http://dx.doi.org/10.1002/jps.2600561005] [PMID: 6059440]
[34]
Higuchi, T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci., 1963, 52, 1145-1149.
[http://dx.doi.org/10.1002/jps.2600521210] [PMID: 14088963]
[35]
Niebergall, P.J.; Milosovich, G.; Goyan, J.E. Dissolution rate studies. II. Dissolution of particles under conditions of rapid agitation. J. Pharm. Sci., 1963, 52, 236-241.
[http://dx.doi.org/10.1002/jps.2600520310] [PMID: 13938476]
[36]
Korsmeyer, R.W.; Gurny, R.; Doelker, E.M.; Buri, P.; Peppas, N.A. Mechanism of solute release from porous hydrophilic polymers. Int. J. Pharm., 1983, 15, 25-35.
[http://dx.doi.org/10.1016/0378-5173(83)90064-9]
[37]
Costa, P.; Sousa Lobo, J.M. Modeling and comparison of dissolution profiles. Eur. J. Pharm. Sci., 2001, 13(2), 123-133.
[http://dx.doi.org/10.1016/S0928-0987(01)00095-1] [PMID: 11297896]
[38]
Rahman, Z.; Zidan, A.S.; Samy, R.; Sayeed, V.A.; Khan, M.A. Improvement of physicochemical properties of an antiepileptic drug by salt engineering. AAPS PharmSciTech, 2012, 13(3), 793-801.
[http://dx.doi.org/10.1208/s12249-012-9800-9] [PMID: 22588676]
[39]
Ramya, T.; Ramkumaar, G.R.; Gunasekaran, S. Structural and qualitative analysis of lamotrigine. Int. J. Neurorehabil., 2014, 1(4), 1-4.
[40]
B, M.; N, A.; S, T. Investigation of formulation variables affecting the properties of lamotrigine nanosuspension using fractional factorial design. Daru, 2010, 18(1), 1-8.
[PMID: 22615586]
[41]
Zohuriaan, M.J.; Shokrolahi, F. Thermal studies on natural and modified gums. Polym. Test., 2004, 23, 575-579.
[http://dx.doi.org/10.1016/j.polymertesting.2003.11.001]
[42]
Kulkarni, R.V.; Mangond, B.S.; Mutalik, S.; Sa, B. Interpenetrating polymer network microcapsules of gellan gum and egg albumin entrapped with diltiazem–resin complex for controlled release application. Carbohydr. Polym., 2011, 83, 1001-1007.
[http://dx.doi.org/10.1016/j.carbpol.2010.09.017]
[43]
Nandi, G.; Patra, P.; Priyadarshini, R.; Kaity, S.; Ghosh, L.K. Synthesis, characterization and evaluation of methacrylamide grafted gellan as sustained release tablet matrix. Int. J. Biol. Macromol., 2015, 72, 965-974.
[http://dx.doi.org/10.1016/j.ijbiomac.2014.09.052] [PMID: 25316428]

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